The projects consist of 5 different, although closely interwoven parts. (1) We plan to continue our exploration of the animal and human organism with respect to the occurrence of monoamine oxidase, types A and B, and to find convenient sources for their isolation. (2) The mechanism of the 2 enzymes will be investigated by studying their substrate and inhibitor patterns and by analyzing the kinetics of degradation and inhibition with stopped-flow spectrophotometry. (3) We will continue to modulate cerebral MAO, and to search for changes in animal behavior and amine metabolism in goldfish and rats. We expect to test our present concept regarding the involvement of a dopaminergic system in operationally defined learning and memory processes. (4) We expect to characterize the A- and B-types of human brain MAO and to compare them with the analogous types in human platelets (B) and placenta (A and B). The determination of platelet MAO will be refined in order to assess, in psychiatric patients, not only quantitative, but also qualitative alterations. We will look for a general pattern of MAO deviations in certain psychotic patients and will investigate whether these alterations can be correlated with the pathologic processes. (5) We previously suggested that behavioral changes induced by us in goldfish and rat by mescaline administration appeared to be due to disturbances in a dopaminergic system. Furthermore, data collected from the literature indicate that mescaline-treated monkeys displayed symptoms which could be interpreted as being caused by a central dopamine deficiency. For these reasons we plan to study several motoric and cognitive functions in volunteers who will be treated with mescaline. The results of these analyses, combined with evaluations of the volunteers' dopamine metabolism, should decide whether there is any relationship of the mescaline-induced syndrome with parkinsonism.